Research

My laboratory-based research programme explores a link between alternative pre-mRNA splicing (AS), a ubiquitous post-transcriptional gene regulatory mechanism, and prostate cancer (PCa) phenotypes.  During AS, coding (exons) and non-coding (introns) regions of a gene are shuffled to create protein isoforms with different functions.  AS is regulated by trans-acting RNA-binding proteins (RBPs), and tightly coupled to transcription. We are studying the link between dysregulation of transcriptional and intracellular signalling processes and AS, mediated by RBPs. 

Our translational research examines how blood-derived liquid biopsy molecular biomarkers can be used to improve treatment outcomes for PCa patients. With NHS colleagues, we are investigating minimally-invasive surgical alternatives to chemotherapy for metastatic testicular cancer to reduce the therapy burden and toxicity. In collaboration with the Wolfson Institute of Preventative Medicine, we are exploring how minimally-toxic chemo-preventative strategies may reduce PCa progression on active surveillance.

Other Activities

• 2019 to date- Member: National Cancer Research Institute (NCRI) Teenage & Young Adults (TYA) and Germ Cell Tumours Clinical Studies Group (CSG) (Germ Cell Tumours Subgroup)
• 2019 to date- Member: NCRI Prostate Cancer CSG (Advanced Disease Subgroup)

Major Funding

• 2020-2021- CRUK Barts Centre Development Fund, Exploiting PTEN loss in Hypoxic Tumour Cells (Principal Investigator), £10,000

• 2018-2021- QMUL Life Sciences Initiative PhD Studentship, Understanding alternative splicing in human cancer by proteomics informed by transcriptomics (PIT) (Co-applicant with Professor Conrad Bessant), ~£80,000

• 2017-2021- The Urology Foundation/The John Black Charitable Foundation Project Grant, Androgen receptor splice variants in prostate cancer (Principal Investigator), £249,999
• 2013-2019- Royal College of Surgeons of England/Cancer Research UK- Clinician Scientist Fellowship in Surgery, Analysis of alternative splicing in prostate cancer metastasis regulated by the RNA-binding proteins Sam68 and hnRNP A2/B1 (Principal Investigator), >£800,000

Recent Publications

Identification of altered biological processes in heterogeneous RNA-sequencing data by discretization of expression profiles Lauria A, Peirone S, Giudice MD et al. Nucleic Acids Research (2020) 48(7) 1730-1747

Reply by Authors Xu L, Mao X, Grey A et al. The Journal of urology (2020) 203(1) 81-82

Elevated driver mutational burden or number of perturbed pathways and poor response to abiraterone or enzalutamide in metastatic castration-resistant prostate cancer De Laere B, Crippa A, Ghysel C et al. ANNALS OF ONCOLOGY (2019) 30(11)
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000491295500319&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=612ae0d773dcbdba3046f6df545e9f6a

Noninvasive Detection of Clinically Significant Prostate Cancer Using Circulating Tumor Cells. Xu L, Mao X, Grey A et al. The Journal of Urology 203(1) 101097JU000000000000-101097JU000000000000
https://www.ncbi.nlm.nih.gov/pubmed/31389764

Investigation of plasma exosomal miRNA as a biomarker and its potential function in prostate cancer castration resistant development Guo T, Wang Y, Mao X et al. CANCER RESEARCH (2019) 79(11)
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000488129901075&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=612ae0d773dcbdba3046f6df545e9f6a

Pathological Findings and Magnetic Resonance Imaging Concordance at Salvage Radical Prostatectomy for Local Recurrence following Partial Ablation Using High Intensity Focused Ultrasound. Thompson JE, Sridhar AN, Tan WS et al. J Urol (2019) 201(1) 1134-1143
https://www.ncbi.nlm.nih.gov/pubmed/30730409

Androgen Receptor Burden and Poor Response to Abiraterone or Enzalutamide in TP53 Wild-Type Metastatic Castration-Resistant Prostate Cancer. De Laere B, Rajan P, Grönberg H et al. JAMA Oncol (2019) (1)
https://www.ncbi.nlm.nih.gov/pubmed/31046065

PEOPLE: PatiEnt prOstate samPLes for rEsearch, a tissue collection pathway utilizing magnetic resonance imaging data to target tumor and benign tissue in fresh radical prostatectomy specimens Heavey S, Costa H, Pye H et al. Prostate (2019) 79(7) 768-777

TP53 outperforms other androgen receptor biomarkers to predict abiraterone or enzalutamide outcome in metastatic castration-resistant prostate cancer De Laere B, Oeyen S, Mayrhofer M et al. Clinical Cancer Research (2019) 25(7) 1766-1773

Cell-free DNA profiling of metastatic prostate cancer reveals microsatellite instability, structural rearrangements and clonal hematopoiesis Mayrhofer M, De Laere B, Whitington T et al. Genome Medicine (2018) 10(7)

Team

Postdoctoral Researchers
Dr John Foster

Biography

Key qualifications